Imunoexpressão de proteínas de checkpoint imune (PD-1, PD-L1 e PD-L2) em lesões de células gigantes

Abstract

Giant cell lesions correspond to a group of pathological processes, with varied biological behaviors, constituted by mononucleated cells (MC) and osteoclast-like multinucleated giant cells (MGC). Despite advances in understanding of the pathogenesis of some members of this group, including central giant cell lesion (CGCL), peripheral giant cell lesion (PGCL) and giant cell tumor (GCT), many aspects of this process remain incompletely understood. Recent research has demonstrated the involvement of immune checkpoint components, particularly programmed cell death protein 1 (PD-1) and its ligands programmed death-ligand 1 (PD-L1) and 2 (PD-L2), in osteoclastogenesis. Despite this evidence, little is known about the role these proteins in the pathogenesis of giant cell lesions. Therefore, this study evaluated the immunoexpression of PD-1, PD-L1 and PD-L2 in CGCL, PGCL and GCT. The sample consisted of 20 cases of CGCL (10 non-aggressive and 10 aggressive), 10 cases of PGCL and 10 cases of GCT. Only CGCL cases with clinical and radiographic information allowing classification as aggressive or non-aggressive (Chuong et al., 1986) were included. In the immunohistochemical study, the percentages of positive MC, non-cannibalistic MGC and cannibalistic MGC (cytoplasm and nucleus) were established in 5 fields of greatest immunoreactivity (400x). The data obtained were statistically analyzed using the Mann Whitney and Spearman correlation tests (p < 0.05). Cytoplasmatic immunoexpression of PD- 1, PD-L1 and PD-L2 in MC was observed in all groups, except for PD-1 (n = 9, 90%). For PD-L1, the median percentages were higher in GCT compared to other groups (p < 0.001). For PD-L2, greater immunoreactivity was observed in PGCL versus GCT (p = 0.049). In non-cannibalistic and cannibalistic MGC, high median percentages were observed in all groups. For PD-1 and PD-L1 in non-cannibalistic MGC, GCT showed higher immunoexpression compared to other groups (p < 0.05). For PD-L2, greater immunopositivity was visualized in non-aggressive CGCL compared to GCT (p = 0.010). Regarding nuclear expression, all groups showed low median percentages and were analyzed descriptively. Statistically significant negative correlations were observed between the immunoexpressions of PD-1 and PD-L1 in cannibalistic MGC of aggressive CGCL (r = -0.648; p = 0.043). Similarly, in the same group, a correlation was found between the expressions of PD-1 in non-cannibalistic MGC and PD-L1 in cannibalistic MGC (r = -0.691; p = 0.027). In non-aggressive CGCL, a statiscally significant positive correlation between PD-1 in cannibalistic MGC and PD-L2 in non-cannibalistic MGC (r = 0.658; p = 0,029). In conclusion, the results of this study suggest a potential involvement of the proteins PD-1, PD-L1 and PD-L2 in the pathogenesis of CGCL, PGCL and GCT. However, the differences in the biological behavior of aggressive and non-aggressive CGCL seem not to be related to the expression of these immune checkpoint proteins. On the other hand, the higher expression of PD-1 and PD-L1 in non-cannibalistic MGC, along with overexpression of PD-L1 in MC, might contribute to the more aggressive behavior of GCT.